Mettl3-mediated mRNA m⁶A modification controls postnatal liver development by modulating the transcription factor Hnf4a.

ABSTRACT: Hepatic specification and functional maturation are tightly controlled throughout development. N6-methyladenosine (m⁶A) is the most abundant RNA modification of eukaryotic mRNAs and is involved in various physiological and pathological processes. However, the function of m⁶A in liver development remains elusive. Here we dissect the role of Mettl3-mediated m⁶A modification in postnatal liver development and homeostasis. Knocking out Mettl3 perinatally with Alb-Cre (Mettl3 cKO) induces apoptosis and steatosis of hepatocytes, results in severe liver injury, and finally leads to postnatal lethality within 7 weeks. m⁶A-RIP sequencing and RNA-sequencing reveal that mRNAs of a series of crucial liver-enriched transcription factors are modified by m

SUBMITTER: Xu Y 

PROVIDER: S-EPMC9355946 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature